I am a pulmonary immunologist with over 20 years of experience in studies of inflammatory/infectious diseases in the lungs and at the systemic level. Sixteen of those years, I have worked at the Ann Arbor VAHS. My overall career goal is to expand the understanding of host pathogen interactions, specifically the effect of microbe- and host-derived signals on the fate of the immune response. I deeply believe that an understanding of these interactions will create a foundation for the development of safe and effective immunomodulatory therapies that will greatly enhance the effectiveness of antimicrobial therapeutics in persistent infections. Our lab has specialized in animal modeling and translational studies applying these principles, which are highly relevant to broader range of diseases as shown by more recent clinical data. Over the last 15 years, my studies have mostly focused on host pathogen interactions between invasive fungus C. neoformans and the mammalian immune system. The studies of invasive fungal infections are of specific interest to the VA, because of the higher than average rate of immunocompromised patients among veterans and increased risk of exposure to various endemic and environmental fungi due to locations and conditions of military service that favor fungal exposures. Unfortunately, the invasive fungal infections have unacceptably high mortality rates, due to limited effectiveness of antifungal drugs, toxicity, and the high potential of fungal organisms to develop resistance to these drugs. Thus, it is crucial to understand the effects of immunomodulation on fungal disease from the perspective of the natural mechanisms of host defenses, mechanisms of immune evasion exhibited by fungi, and to explore pre-clinical approaches of immuno-modulatory therapies. The long-standing support of VA BLR&D was one of the crucial factors that allowed our group to establish itself among leaders in cryptococcal and fungal immunology. While this support has led to many important findings, there is still a lot more that we need to learn before we can safely and efficiently apply immunomodulatory therapies in persistent infections. The VA RCS Award will allow our group to continue this great work and create stability supportive of exploration of very novel but more risky directions of research. This award will also allow to further broaden PI?s collaborative interactions with physician scientists, enhance training efforts, and to continue PI?s service to the scientific community at the VA and beyond.